Vaccines Protect Monkeys Against Ebola and Marburg Viruses

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This study has found while these two vaccines proved highly effective in protecting against Ebola and Marburg viruses, the researchers say they are still two to three years away from beginning human studies.

Assure patients that the Ebola and Marburg viruses currently pose no major threat to the general population.

WINNIPEG, June 6-Two experimental vaccines have been found to be 100% effective in protecting monkeys from the Ebola and Marburg viruses, suggesting human vaccines down the road.

It only took a single dose of either vaccine to immunize the animals against one virus or the other, Canadian and American researchers reported online in the June issue of Nature Medicine. Both viruses induce hemorrhagic fever in monkeys and humans.

"The vaccines seem to induce immunity very rapidly," said immunopathologist Steven M. Jones, Ph.D., of the National Microbiology Laboratory of the Public Health Agency of Canada here. "They have applicability within the lifetime of outbreak."

In the world of vaccine development, there are numerous false starts, Dr. Jones said. What appeared to be so promising about these vaccines was that they triggered such quick immunity with just a single shot.

Dr. Jones said that human forms of the experimental vaccines will not be ready for initial testing for at least another two to three years.

Meanwhile, the death toll from the world's worst Marburg outbreak has claimed 340 lives, many of them children, in remote northwest Angola and has sickened a total of 408. Marburg and Ebola both come from the Filoviridae family and can cause hemorrhagic fever. They are both highly contagious pathogens transmitted through fluids. Currently, there is no vaccine or cure for either disease.

Dr. Jones, along with colleagues from the U.S. Army Medical Research Institute of Infectious Diseases in Frederick, MD., divided 12 macaque monkeys into groups. Six animals received the Ebola vaccine while the remaining six received the Marburg vaccine.

The vaccines contained a live attenuated recombinant vesicular stomatitis virus (rVSV), a pathogen of similar genetic structure to Ebola and Marburg. VSV is relatively harmless to humans, although it can cause mouth disease in cattle. The research team removed genetic material from the vesicular stomatitis virus and replaced it with DNA from either the Marburg or Ebola viruses. The transplanted genetic material forced V.S.V. to express Marburg or
Ebola proteins on its surface. The proteins do not cause illness, but
they provoked an immune response that protected the animals.

Both groups of macaques (monkeys) received a single intramuscular injection on day one of the trial. None of the animals showed any clinical symptoms during the first four weeks of the study, indicating the two vaccines were safe. Blood samples taken after immunization also showed no traces of vesicular stomatitis virus replication or shedding from the animals.

On day 28, the animals were challenged with either injections of high doses of Ebola virus or Marburg. Two animals from each group served as challenge controls. Two macaques that had previously been inoculated against Marburg received a high dose of an Ebola strain while two Ebola-vaccinated creatures received a high dose of a Marburg strain. The remaining four Marburg-vaccinated animals were injected with the Marburg strain while the remaining Ebola-vaccinated animals were injected with the Ebola strain.

The two Marburg-vaccinated animals exposed to Ebola showed clinical signs of disease by day three after the challenge and died on day six. The Ebola-vaccinated animals exposed to Marburg experienced symptoms on day four after the challenge and died on day nine.

However, the remaining eight animals showed no signs of illness, indicating the vaccines had successfully protected them.

"You wouldn't otherwise have known they had been infected with these lethal diseases," Dr. Jones said.

In the third part of the study, Dr. Jones and colleagues tested whether the vaccines could protect against different strains of the Ebola and Marburg vaccines. So 113 days after the second phase of the study, the scientists injected a strain called Marburg-Popp into the remaining four Marburg-vaccinated animals. And 234 days after the study's second phase, the researchers injected a strain of Ebola virus called Sudan Ebola into the Ebola-inoculated animals.

All four of the Marburg-vaccinated animals survived and showed no clinical symptoms. However, three of the four Ebola-vaccinated animals died after exposure to the Sudan-Ebola strain.

This finding "indicates you need to have more than one form for the vaccines for Ebola," Dr. Jones said. "They have to be species specific."

The investigators were encouraged by the success of the virus vectors. Previous research on Ebola and Marburg vaccine testing looked at adenoviruses as vectors. However, the problem with that is that many people are exposed to adenoviruses, which could compromise the effectiveness of an adenovirus-based vaccine.

Dr. Jones said there "there are alternative adenovirus vectors that can be used," which are more rare and could be effective. But what's so appealing about the latest research is that the vectors used here are organisms not commonly found in the general population.